Changing Priorities in Vaccinology: Antibiotic Resistance Moving to the Top

Abstract

Antimicrobial resistance (AMR) is currently the most alarming issue for human health. AMR already causes 700,000 deaths/year. It is estimated that 10 million deaths due to AMR will occur every year after 2050. This equals the number of people dying of cancer every year in present times. International institutions such as G20, World Bank, World Health Organization (WHO), UN General Assembly, European Union, and the UK and USA governments are calling for new antibiotics. To underline this emergency, a list of antibiotic-resistant “priority pathogens” has been published by WHO. It contains 12 families of bacteria that represent the greatest danger for human health. Resistance to multiple antibiotics is particularly relevant for the Gram-negative bacteria present in the list. The ability of these bacteria to develop mechanisms to resist treatment could be transmitted with genetic material, allowing other bacteria to become drug resistant. Although the search for new antimicrobial drugs remains a top priority, the pipeline for new antibiotics is not promising, and alternative solutions are needed. A possible answer to AMR is vaccination. In fact, while antibiotic resistance emerges rapidly, vaccines can lead to a much longer lasting control of infections. New technologies, such as the high-throughput cloning of human B cells from convalescent or vaccinated people, allow for finding new protective antigens (Ags) that could not be identified with conventional technologies. Antibodies produced by convalescent B cell clones can be screened for their ability to bind, block, and kill bacteria, using novel high-throughput microscopy platforms that rapidly capture digital images, or by conventional technologies such as bactericidal, opsono-phagocytosis and FACS assays. Selected antibodies expressed by recombinant DNA techniques can be used for passive immunization in animal models and tested for protection. Antibodies providing the best protection can be employed to identify new Ags and then used for generating highly specific recombinant Fab fragments. Co-crystallization of Ags bound to Fab fragments will allow us to determine the structure and characteristics of new Ags. This structure-based Ag design will bring to a new generation of vaccines able to target previously elusive infections, thereby offering an effective solution to the problem of AMR.

New immunization strategies: adapting to global challenges

“…A further example of using vaccines in an integrated approach to curb global health threats is the fight against antimicrobial resistance (AMR), currently one of the most alarming issues for human health. Drug resistant infections may already cause 700,000 deaths per year and it is estimated that 10 million deaths due to AMR may occur every year after 2050 [49]. Vaccines can impact antibiotic-resistant infections through a direct reduction in the resistant organisms and strains that are specifically targeted by the vaccine, as well as through a reduction in common illnesses that often lead to the use of antibiotics and therefore selection pressure on pathogens [50].…”

Les vaccins de demain

“…Les sérums recueillis ont ensuite été testés par des techniques Elisa puis en cytométrie en flux afin de détecter les protéines présentes à la surface d'un ensemble de souches de MenB cependant que l'activité bactéricide de ces sérums sur ces souches était testée en parallèle [7]. F. L'épitope d'intérêt est utilisé comme antigène vaccinal charge devaient être rapidement développées (tableau 2) Dans ce document l'OMS souligne le rôle important des vaccins pour essayer de gérer la problématique mondiale que représente l'émergence des bactéries résistantes aux antibiotiques [12]. Au cours de la dernière décennie, l'apparition de nouvelles technologies a permis de renouveler la conception des vaccins conduisant à une approche baptisée « Vaccinologie inverse 2.0 » [8].…”

The Fourth International Neonatal and Maternal Immunization Symposium (INMIS 2017): Toward Integrating Maternal and Infant Immunization Programs

“…Thus, effective vaccines could potentially reduce the numbers of infections, reduce the need for antibiotics, reduce the emergence of resistant strains, and improve prevention of resistant strains. Theoretically, a vaccine could be used to target determinants of antibiotic resistance, and vaccines against important Gram-negative pathogens are already on the horizon (47). The development of monoclonal antibodies (MAbs) at birth is also part of the Bill & Melinda Gates Foundation strategy, whereas prophylactic MAbs could be given to infants determined to be at risk.…”